Radiation therapy (RT), specifically stereotactic radiosurgery (SRS), is frequently used in cancer treatment of localized disease. Emerging evidence provides a rationale for combining SRS with immunotherapy for treatment of incurable metastatic solid tumors. In addition to the direct killing of tumor cells, RT can cause the release of tumor antigens and molecules that promote an anti-tumor immune response. Further, RT can modify the tumor environment to increase the susceptibility of tumor cells for immune attack. We propose to combine RT with two powerful immune modulators, Fms-like tyrosine kinase ligand (Flt3L) and an antibody that activates CD27. Flt3L is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of dendritic cells in blood and tissues. The dendritic cells are critical for the initiation of the anti-tumor immune response. CD27 is key pathway for generating T cell immunity and memory. We will use an antibody that activates CD27 together with Flt3L to investigate the benefits of these immune modulators when combined with RT in mouse models to provide the basis for future clinical studies. By addressing the lack of immune based cancer therapies, our product offers the potential of considerable impact in reducing the toll of cancer.